Description: <b>Natural compound</b> found in apples and rosemary.<br>
Ursolic acid (UA) is a pentacyclic triterpenoid found in many plants (notably apple peel, rosemary, thyme, holy basil, and other herbs). In cancer models it is best described as a multi-target signaling modulator with prominent effects on NF-κB inflammation/survival transcription, STAT3, PI3K/AKT/mTOR, and MAPK pathways, with downstream outcomes including cell-cycle arrest, apoptosis, anti-angiogenesis, and reduced invasion/EMT. A practical translational constraint is poor aqueous solubility and low oral bioavailability, so many strong in-vitro µM effects may not map cleanly to typical oral exposure without formulation.<br>
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<!-- Ursolic Acid (UA) — Time-Scale Flagged Pathway Table (web-page ready) -->
<table border="1" cellpadding="4" cellspacing="0">
<tr>
<th>Rank</th>
<th>Pathway / Axis</th>
<th>Cancer Cells</th>
<th>Normal Cells</th>
<th>TSF</th>
<th>Primary Effect</th>
<th>Notes / Interpretation</th>
</tr>
<tr>
<td>1</td>
<td>NF-κB inflammatory / survival transcription</td>
<td>NF-κB ↓; COX-2/iNOS/cytokines/Bcl-2 family/MMPs ↓ (reported)</td>
<td>Inflammation tone ↓ (context)</td>
<td>R, G</td>
<td>Anti-inflammatory + anti-survival transcription</td>
<td>One of the most frequently reported UA effects across tumor models; downstream impacts include reduced pro-survival and pro-metastatic gene programs.</td>
</tr>
<tr>
<td>2</td>
<td>STAT3 axis (JAK/STAT3 signaling)</td>
<td>STAT3 activity ↓ (reported); downstream targets ↓</td>
<td>↔</td>
<td>R, G</td>
<td>Oncogenic transcription suppression</td>
<td>UA is often reported to suppress STAT3 signaling, contributing to reduced proliferation/survival signaling.</td>
</tr>
<tr>
<td>3</td>
<td>PI3K → AKT (± mTOR) survival axis</td>
<td>PI3K/AKT ↓; mTORC1 tone ↓ (reported; model-dependent)</td>
<td>↔</td>
<td>R, G</td>
<td>Growth/survival modulation</td>
<td>Commonly listed mechanism; direction and strength vary by cell line and exposure.</td>
</tr>
<tr>
<td>4</td>
<td>MAPK re-wiring (ERK / JNK / p38)</td>
<td>Stress-MAPK modulation (context-dependent)</td>
<td>↔</td>
<td>P, R, G</td>
<td>Signal reprogramming</td>
<td>JNK/p38 activation and ERK modulation are reported variably; avoid fixed arrows unless tied to a specific model.</td>
</tr>
<tr>
<td>5</td>
<td>Cell-cycle checkpoints (Cyclins/CDKs; p21/p27)</td>
<td>Cell-cycle arrest ↑ (G1/S or G2/M; reported); Cyclin D1/CDKs ↓ (context)</td>
<td>↔</td>
<td>G</td>
<td>Cytostasis</td>
<td>Often downstream of NF-κB/STAT3/PI3K signaling suppression.</td>
</tr>
<tr>
<td>6</td>
<td>Intrinsic apoptosis (mitochondrial/caspase linked)</td>
<td>Apoptosis ↑; Bax ↑; Bcl-2 ↓; caspases ↑ (reported)</td>
<td>↔ (generally less activation)</td>
<td>G</td>
<td>Cell death execution</td>
<td>Common downstream endpoint; can be coupled to stress signaling and survival pathway suppression.</td>
</tr>
<tr>
<td>7</td>
<td>Angiogenesis signaling (VEGF / HIF-1α outputs)</td>
<td>VEGF ↓; angiogenic outputs ↓ (reported)</td>
<td>↔</td>
<td>G</td>
<td>Anti-angiogenic support</td>
<td>Typically phenotype-level effects tied to NF-κB/PI3K/HIF programs.</td>
</tr>
<tr>
<td>8</td>
<td>Invasion / metastasis programs (MMPs / EMT)</td>
<td>MMP2/MMP9 ↓; EMT markers ↓; migration/invasion ↓ (reported)</td>
<td>↔</td>
<td>G</td>
<td>Anti-invasive phenotype</td>
<td>Often downstream of NF-κB/STAT3 changes; not universal across all tumors.</td>
</tr>
<tr>
<td>9</td>
<td>ROS / redox modulation</td>
<td>ROS direction variable; redox stress or buffering reported (context)</td>
<td>Oxidative injury ↓ in some non-tumor stress models</td>
<td>P, R, G</td>
<td>Stress modulation</td>
<td>UA is not a reliable “pro-oxidant killer”; redox effects depend on dose, model, and baseline oxidative state.</td>
</tr>
<tr>
<td>10</td>
<td>Bioavailability / formulation constraint</td>
<td>Systemic exposure often limited (poor solubility)</td>
<td>—</td>
<td>—</td>
<td>Translation constraint</td>
<td>UA is highly lipophilic with poor aqueous solubility; many formulations (e.g., nanoparticles, phospholipid complexes) are explored to improve exposure.</td>
</tr>
</table>
<p><b>Time-Scale Flag (TSF):</b> P / R / G</p>
<ul>
<li><b>P</b>: 0–30 min (rapid signaling interactions)</li>
<li><b>R</b>: 30 min–3 hr (acute stress-response + transcription signaling shifts)</li>
<li><b>G</b>: >3 hr (gene-regulatory adaptation and phenotype-level outcomes)</li>
</ul>